We have used monoclonal antibodies against a normal differentiation antigen to treat mouse leukemias. In those studies, treatment of a transplanted T cell leukemia with monoclonal antibody against the Thy 1 differentiation antigen induced prolonged survival and cure in a significant proportion of mice. It also led to a modest but significant prolongation of chemotherapy induced remissions in mice with spontaneous lymphoid malignancies. The purpose of the proposed studies is to evaluate the use of monoclonal anti-Thy 1.1 antibodies for the therapy of transplanted and spontaneous neoplastic disease in mice. The influence of the clearance rates, biodistribution, and avidity of monoclonal antibodies of each immunoglobulin subclass will be determined, as well as their interaction with effector cells. Combinations of antibodies against different T cell determinants will be used in an attempt to prevent the emergence of antigen negative tumor cell variants. The results of these studies should help elucidate the principles governing monoclonal antibody therapy and facilitate optimal design of future clinical trials in humans.